A calcium manganese-based pancatalytic nanozyme as a cell pyroptosis inhibitor for efficient inflammatory bowel disease treatment

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder marked by dysregulated immune responses and pyroptosis of intestinal epithelial cells, a type of programmed cell death that aggravates inflammation. Current therapeutic strategies frequently encounter limitations in both efficacy and specificity. Herein, we developed a calcium manganese-based (CaMn₂O₄) pancatalytic nanozyme designed to mitigate pyroptosis and alleviate IBD symptoms. The calcium manganese-based nanozyme exhibits dual enzyme (catalase and superoxide dismutase)-mimetic catalytic activities, scavenging reactive oxygen species and suppressing GSDMD cleavage, a key mediator of pyroptosis. In vitro studies demonstrated that the CaMn₂O₄ nanozyme significantly reduced pyroptotic cell death in lipopolysaccharide (LPS)/nigericin (Ni)-stimulated cells. In a murine colitis model, CaMn₂O₄-based nanozyme treatment attenuated inflammatory infiltration, preserved epithelial barrier integrity, and downregulated pyroptosis-related markers. This study highlights the potential of pancatalytic nanotherapy targeting pyroptosis as a novel strategy for IBD treatment.